Single nucleotide polymorphisms in MDR1 gen correlates with outcome in advanced non-small-cell lung cancer patients treated with cisplatin plus vinorelbine

N. Viñolas, M. Provencio, N. Reguart, F. Cardenal, V. Alberola, J. M. Sánchez-Torres, F. J. Barón, M. Cobo, I. Maestu, I. Moreno, C. Mesía, A. Izquierdo, E. Felip, M. López-Brea, A. Márquez, M. Sánchez-Ronco, M. Tarón, M. C. Santarpia, R. Rosell

Research output: Contribution to journalArticle

Abstract

New therapeutic approaches are being developed based on the findings that several genetic abnormalities underlying NSCLC could influence chemosensitivity. In this study, we assessed whether the presence of polymorphisms in ERCC1, XPD, RRM1 and MDR1 genes can affect the efficacy and the tolerability of cisplatin and vinorelbine in NSCLC patients. Material and methods: Eligible patients had histological confirmed stage IV or IIIB (with malignant pleural effusion) non-small-cell lung cancer (NSCLC) previously untreated with chemotherapy; World Health Organization performance status (PS) 0-1. Patients received intravenous doses of vinorelbine 25mg/m 2 on day 1 and 8 and cisplatin 75mg/m 2 on day 1, every 21 days, for a maximum of eight cycles. Results: 94 patients were included. Median age was 61 years; 84% were male; WHO performance status (PS) was 0 in 24%; and 88% of patients had stage IV disease. The median number of cycles was 6. Overall median survival was 10.92 months (95% CI 9.0-12.9). Overall median time to progression was 5.89 months (95% CI 5.2-6.6).Results of the multivariate analysis for time to progression showed that ECOG 0 (hazard ratio [HR] ECOG 1 vs. ECOG 0, 1.74; p = 0.036), MDR13435CC (HR CT vs. CC, 2.01; p = 0.017; HR TT vs. CC, 1.54; p = 0.22), and decreasing age (HR of age, 0.97; p = 0.016) were the most powerful prognostic factors significantly related to lower risk of progression. Whereas ECOG 0 was the only prognostic factor for survival (HR ECOG 1 vs. ECOG 0, 3.02; p = 0.001).There was no significant association between any of the SNPs analysed and the occurrence of vinorelbine and cisplatin-related toxicity. Conclusion: In our results, the most important prognostic factors associated with lower risk of progression were MDR1 3435 CC genotype, PS 0 and younger age.

Original languageEnglish
Pages (from-to)191-198
Number of pages8
JournalLung Cancer
Volume71
Issue number2
DOIs
Publication statusPublished - Feb 2011

Keywords

  • Cisplatin
  • Genomics
  • Non-small-cell lung cancer
  • Vinorelbine

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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    Viñolas, N., Provencio, M., Reguart, N., Cardenal, F., Alberola, V., Sánchez-Torres, J. M., Barón, F. J., Cobo, M., Maestu, I., Moreno, I., Mesía, C., Izquierdo, A., Felip, E., López-Brea, M., Márquez, A., Sánchez-Ronco, M., Tarón, M., Santarpia, M. C., & Rosell, R. (2011). Single nucleotide polymorphisms in MDR1 gen correlates with outcome in advanced non-small-cell lung cancer patients treated with cisplatin plus vinorelbine. Lung Cancer, 71(2), 191-198. https://doi.org/10.1016/j.lungcan.2010.05.005